The general objective of this project is the development of methods for the exposure of the details of enzymic reactions by use of the heavy-atom kinetic isotope effect. Specific objectives for the next budget period are: Completion of the modeling phase (experiments are completed) of a study of the symmetry-destroying H atom transfer in the pyrolysis of dimethyl ether, via the inter- and intra-molecular C13 isotope effects. Completion of the modelling phase (experiments are completed) of a study of the C13 inter- and intra-molecular isotope effects in the decarboxylation of oxalic acid in dioxane solution. Completion of experiments designed to measure the C13 isotope effects in the decarboxylation of malonic acid in water solution. To advance computational experiments on a simplified enzyme-plus- substrate model to establish the influence on kinetic isotope effects arising in the reaction of: the strength of the enzyme-substrate interaction, the geometry of the complex, and the composition of the reaction coordinate eigenvector.